This invention relates to liquid chromatography columns.
Cartridges for use in liquid chromatography are known in which a flow distributor and a flow collector are located in the vicinity of the end caps of the cartridge to distribute and collect the process fluid.
The invention features, in general, a chromatography cartridge assembly including a cartridge and a first end cap. A wall of the cartridge defines a chamber for containing chromatography media. The first end cap is positioned within a first end cap receiving opening of the cartridge. The first end cap defining a passage for flow of process fluid. A clamp is circumferentially located about the cartridge wall for applying a radial load through the wall to the end cap to fix the end cap in a desired position.
In preferred embodiments, a second end cap is positioned within a second end cap receiving opening of the cartridge. The second end cap defines a passage for flow of process fluid. A clamp is circumferentially located about the cartridge wall for applying a radial load to the second end cap to fix the second end cap in a desired position.
The first end cap includes flow distributor passages for distributing process fluid across a cross-sectional area of the chamber, and the second end cap includes flow collector passages for collecting process fluid from across a cross-sectional area of the chamber.
The inner surface of the wall has a constant diameter. Alternatively, the inner surface of the wall defines a section of constant inner diameter for slidably receiving the first end cap, and a circumferential groove for receiving the second end cap. Alternatively, the second unitary end cap is integral with the cartridge.
The end caps each include a sieve for retaining the chromatography media in the chamber. The sieve includes a fine mesh and a course mesh.
Flexible seals are located between the end caps and the wall of the cartridge. The first and second end caps each include a connector for attachment to an inlet conduit and an outlet conduit, respectively.
A support clamp holds the cartridge. The cartridge includes a flexible wall configured to radially compress the chromatography media. The chromatography media is a hydrophilic material. The chromatography media has an operating pressure rating greater than about 3 bar. The chromatography media has a particle size in the range of about 15-200 microns.
According to another aspect of the invention, a chromatography apparatus includes a cartridge assembly and a compression module surrounding the cartridge assembly. The compression module defines a pressure chamber for containing a pressurized fluid. The pressurized fluid acts to move a flexible wall of the cartridge.
According to another aspect of the invention, a method of revitalizing a packed column having trapped air includes providing a chromatography cartridge including a flexible wall defining a chamber. The flexible wall forms a movable diaphragm for compressing chromatography media located within the chamber. Compression is applied to the chromatography media to minimize the volume of trapped air.
In preferred embodiments, the compression is radial compression.
According to another aspect of the invention, a method of sealing a flexible-walled tube includes placing a sealing member within the tube, positioning a first conical member around the outside of the tube and axially aligned with the sealing member, and positioning a second conical member around the outside of the tube and in contact with the first conical member. An axial load is applied to the second conical member, whereby the axial load on the second conical member acts to radially compress the first conical member. The radial compression causes permanent deformation of the first conical member and the adjacent wall of the tube to seal the sealing member within the tube. The seal is maintained upon removal of the axial load.
In preferred embodiments, the sealing member is an end cap defining an inlet passage for flow of process fluid and flow distributor passages for distributing process fluid across a cross-sectional area of the tube.
According to another aspect of the invention, a clamping mechanism for sealing a sealing member within a tube includes a first conical member for placement around the outside of the tube, a second conical member for placement around the outside of the tube and in contact with the first conical member, and a load applicator for applying an axial load to the second conical member. The axial load on the second conical member acts to radially compress the first conical member. The radial compression causes permanent deformation of the first conical member and the adjacent wall of the tube to seal the sealing member within the tube.
According to another aspect of the invention, a chromatography column includes a column having a flexible-wall. The column contains chromatography media. An end cap is positioned within the column and defining an inlet passage for flow of process fluid and flow distributor passages for distributing process fluid across a cross-sectional area of the column. A clamp is located around an outside of the column for sealing the end cap within the column.
In preferred embodiments, the clamp radially compresses the flexible wall to seal the end cap within the column. The clamp is a conical member.
Advantages include a cartridge which can be dynamically compressed and used as a stand alone device. The cartridge is disposable and provides convenience over glass columns which the user packs themselves. The cartridge seals are static and thus easier to clean between runs than the dynamic seals in a glass column.
Additional advantages include liquid chromatography of biomolecule process fluids under pressures above 3 bar. The materials used in the chromatography apparatus prevent biomolecule precipitation and non-specific adsorption. The cartridge within a module system permits changeout of wetted components and reuse of the module for different biomolecules without cross-contamination.
Other advantages and features of the invention will ba apparent from the following description of a preferred embodiment thereof and from the claims.